News from the Medical Research Council March / April 2009

Developing the drugs of the future The MRCT Centre for Therapeutic Discovery page 2

Profile: The Gray Institute for Radiation, Oncology and , Oxford page 10 3 MARCH/APRIL 2009 Update from CONTENTS Developing the the MRC Chief drugs of the future Executive 03  Update from the MRC Chief Executive A new centre that will speed the discovery and Sir added: “This centre of national The announcement 04 Opening a window on development of drugs in the UK has been established excellence, in forming partnerships with academia, will that a UK Centre for MRC research provide a focus of knowledge and expertise. The initiative Therapeutic Discovery in London, jointly funded by the MRC and MRC has been created, led by 05 Industry update will benefit patients in the UK and around the world. It Technology. will also support innovation and provide a training ground MRC Technology, is very 06 Securing skills today for for the next generation of scientists across Britain. It is welcome news in this time tomorrow’s scientists The MRCT Centre for Therapeutic Discovery launched in April, will these types of projects which represent the seed corn of of economic turmoil. I was heartened to take advantage of the UK’s high quality academic research to discover the future UK economy by enhancing the UK’s leadership hear the Prime Minister’s recent comments that 10 Profile: The Gray and develop drugs for areas of unmet need. Using state-of-the-art the economy needs to shift from its dependence Institute for Radiation, position in the scientific and technical disciplines of early computational and medicinal chemistry it will produce drug-like molecules on financial services towards science and Oncology and Biology, stage medicine discovery.” Oxford with potential to become treatments. New antibody therapies will also be technology. Investment in the UK’s scientific developed by the centre, taking advantage of MRC Technology’s expertise Dr Justin Bryans, Director of Drug Discovery at MRC excellence is crucial now, perhaps more than ever 16 MRC People in ‘humanising’ antibodies - the process of genetically modifying rodent Technology, explained that the centre will provide “a forum before, because it is the key to economic recovery. antibodies to make them more like human ones. 18 Hopping across for education and training in the field of medicines research”, disciplines solves creating skilled jobs in medicinal chemistry and bioscience. Moving forward, a broad discussion is needed research puzzle MRC Technology’s CEO, Dr David Tapolczay, explained: “For the first time, involving research funders, the Government and UK academics will have a dedicated centre with which to collaborate “Partnering our products with pharmaceutical and the public, about the areas in which we’re likely to and progress their science to deliver tangible clinical benefit. In so doing, biotechnology companies worldwide will increase the value be most successful. Research funding is a balancing this initiative will help the UK to retain its world-leading reputation for of the basic research that we support,” he added. act between investment in ‘blue skies’ research innovation in drug discovery.” and applied research for which the outcome is The centre has an annual operating budget of £6 more visible from the outset. Both are absolutely The aim of the centre is to build on the capabilities and research capacity million, secured from a range of sources including MRC essential because if we don’t support new ideas in of the MRCT Drug Discovery Group. This will provide the UK with translational funding. It will commercialise its products, but all disciplines, very soon nothing is left to translate a national drug discovery resource which has the critical mass to be profits will be re-invested. downstream. And we need excellence in a whole globally competitive. It will establish partnerships with academic scientists range of disciplines in order to make real advances. and industry to take the research towards clinical benefit. For example, on page 18, you can read about a successful interdisciplinary collaboration which has offered unexpected new insights into cancer.

Representatives from the research community met late last year to agree a set of health research opportunities for the UK that target the biggest and most important health challenges we are likely to face over the next decade. This spring we are consulting academic and clinical stakeholders about these research opportunities before they are considered by the OSCHR Board. You can read about the outputs of this meeting on our website ( www.mrc.ac.uk/healthresearch) and contribute to this important discussion by sending us your comments and views – I look forward to hearing them.

Sir Leszek Borysiewicz 5

Opening a window INDUSTRY on MRC research UPDATE Bridging the academic-commercial divide facilities offered by companies. Students also gain an awareness of the drug discovery and development For the first time ever, researchers and Each research project shows a financial value, but it The MRC is putting renewed effort into forging links process and an insight into the some of the scientific between academia and industry this year, with a £3.2 challenges that pharmaceutical companies face.” the public can get a clear picture of the is important to stress that these figures cannot be million investment to create 45 new Industrial CASE research that the MRC funds through a compared across different project types. studentships. Peter Dukes, the MRC’s Head of Research Awards, new interactive online web resource. added: “CASE students act as a bridge, opening up the Tony Peatfield, MRC Senior Responsible Officer The studentships support multi-disciplinary research perspectives of their MRC supervisors and colleagues The MRC Research Portfolio (www.mrc.ac.uk/ for the portfolio, explained: “It’s important to note training projects between industry and academia. to the priorities that drive research in industry and researchportfolio) allows anyone to view research that for grants or fellowships the sum shown is the Students are based at the participating academic increasing opportunities for the translation of research.” currently being funded by the MRC, as well as any whole-life-value, but for a unit/institute programme institution, but spend a minimum of six months at a research projects that have been completed since or partnership/contribution the figure denotes company, learning about how commercial research This year’s CASE intake begins in October 2009 and 1 April 2008. Visitors to the website can find out annual spend. There are also important differences in works and also gaining business-related training in, for will focus on in vivo research. More information on the exactly what research is underway, who is doing it, the funding structures, so these figures can include example, project management or business strategy. scheme is at: and roughly how much money is being spent on it. different components. The financial information www.mrc.ac.uk/Fundingopportunities/Studentships/ shown online is intended as an overview. If users have The studentships focus on building up the research IndustrialCASE/MRC004608 One of the aims of the MRC Research Portfolio is to a specific question about the financial value of what workforce in new or growing areas of science, giving increase the MRC’s accountability and transparency in is being funded in a particular area of science they students a taste of the advanced skills and technologies its use of public funds. should contact the MRC at corporate@headoffice. in industry, and giving them a feel for industry’s mrc.ac.uk to discuss their requirements.” competitive environment. Companies also benefit John Jeans, MRC Chief Operating Officer and from the scheme, gaining from the MRC’s research Deputy Chief Executive, said: “This is a really exciting The MRC Research Portfolio can be found at: excellence, and getting new ideas and insights. development for the MRC. We are keen to throw www.mrc.ac.uk/researchportfolio open the doors on our research and show the Companies involved in the scheme in last year’s public exactly what research their money is funding. intake included Pfizer, Wyeth, GlaxoSmithKline, The portfolio also gives the UK research community UCB Celltech and AstraZeneca. an insight into our research so that they can position AstraZeneca’s Jackie Wilbraham, who is a themselves according to the work that others member of the assessment panel for CASE, is are doing.” enthusiastic about the scheme: “These studentships give students a valuable opportunity to undertake The portfolio contains information on programmes part of their research in the world class research and projects across the whole spectrum of MRC research – from research programmes in institutes, units and centres, to individual project grants and fellowships. Users can browse the portfolio by grant type, status, principal investigator and research organisation, or search the system using key words. Search results can also be filtered, so that users can select the most relevant information. 7

partner institutions. New-blood lecturers and academic Engaging the wider community have been recruited. These include a Pfizer- Informing the wider research community and the public Securing skills today for sponsored Chair in Integrative Biomedicine and ‘3Rs’ about the importance of animal-based research is another lecturer at King’s College, enhancing the profile of in vivo important activity for the centres. Recently, a public tomorrow’s scientists physiology and pharmacology as essential disciplines. discussion on the use of animals in medical research was organised by staff at the University of Glasgow as part of Mike Collis adds: “We are pleased to report that the its Café Scientifique. Meanwhile, both Imperial College and Whole-animal physiology and pharmacology Links with industry potential number of PhD studentships held at the centres the University of Manchester have outreach programmes research in the UK is being boosted with a Launched in 2005 and now in full swing, the programme has already doubled from the original 50 directly funded aimed at school children and Members of Parliament, £12.3 million joint funding initiative to halt has established four university-based integrative through the integrated mammalian biology capacity- which include talks and a tour of their animal facilities. the loss of specialist skills and help forge mammalian biology centres which are acting as ‘honey-pots’ building awards, and we expect the number to increase The centres will outline their research and educational closer links with industry. for public-private funding opportunities. Two of the ‘virtual further over the next three years.” activities at a Scientific Meeting in autumn 2009, which centres’ are based in London at Imperial College and King’s will also include a careers session for students. For further Translation of basic research discoveries into new College, and the other two are joint consortia between In addition, the MRC recently awarded funding to seven information, contact Dr Mike Collis by emailing mc@bps. treatments depends on testing their safety and efficacy the universities of Manchester and Liverpool, and the universities for 22 PhD studentships focused on in vivo ac.uk. More information and links to the four centres are in integrated biological systems, including whole animals. universities of Glasgow and Strathclyde. animal sciences training, some of which were also part- But recently the number of scientists who have the funded by the British Pharmacological Society. And the available in the April 2009 BBSRC Business magazine at www.bbsrc.ac.uk/publications/business specialist skills to perform these studies has been “The capacity building awards are proving to be an MRC and BBSRC have also funded 12 capacity-building declining as established researchers retire, and fewer excellent example of how public and private funding Masters studentships in five universities for in vivo sciences. universities offer whole animal science at undergraduate organisations can work together to rebuild an essential and postgraduate level. area of UK biomedical research,” explains Dr Mike Collis, chairman of the British Pharmacological Society Integrative A capacity-building programme in integrated mammalian Pharmacology Fund, and coordinator of the project. biology has been set up to meet this challenge. The Diabetes study gains the help programme aims to equip researchers from undergraduate For example, the universities of Liverpool and Manchester to postdoctoral level with expertise and skills, such as are hosting the MRC Centre for Drug Safety Science. This of 6,000 volunteers best practice for using animals in research and high centre brings together human genetics and in vivo science quality experimental design. It is jointly funded by the with industrial partners to improve drug design and the A major UK clinical study in the adult- The study, jointly led by Professor Mike Sampson in BBSRC, the British Pharmacological Society (through their screening processes used to minimise the risk of adverse onset form of diabetes passed a significant Norwich and Professor Nick Wareham in , Integrative Pharmacology fund, supported by AstraZeneca, drug reactions. milestone in February, recruiting its 6,000th began in 2003 and aims to recruit 10,000 people. It is GlaxoSmithKline and Pfizer), the Department for volunteer. jointly funded by the MRC and the . Innovation, Universities and Skills, the Higher Education Creating closer links with industry also encourages Funding Council for England, the Scottish Funding Council industrial scientists to get involved in university-based The Norfolk Diabetes Case Control Study is a The announcement coincided with news that UK and the MRC. teaching. Recently AstraZeneca held an experimental collaboration between the MRC Epidemiology Unit Biobank, another major study part-funded by the MRC, design day at King’s College London, while a similar course in Cambridge and the diabetes team at the Norfolk has now reached its halfway mark by recruiting 250,000 held in Manchester will be extended to an annual event and Norwich University Hospital and University of people. UK Biobank relies on the altruism of the UK though industrial sponsorship. East Anglia. public to submit to being questioned, measured and analysed over 30 years in order to build up a major Teaming up on education Dr Claudia Langenberg of the MRC Epidemiology Unit resource to tackle diseases like cancer and heart With their own educational projects and activities now said: “The fantastic response of the people in Norfolk disease. It now expects to recruit its 500,000th person fully established, centres are also starting to work together. to our study has given us a unique opportunity to in mid-2010, ahead of schedule. Imperial College and King’s College London are planning investigate how genes influence the development of to develop a joint state-of-the-art teaching and research Type 2 diabetes and its complications.” facility for telemetry, an in vivo technology which can be used to monitor animals remotely. The technology allows The study has recently contributed to the discovery of for fewer animals to be used for research and minimises a gene that is strongly linked to high blood sugar levels disruption to their normal behaviour. and an increased risk of Type 2 diabetes. The gene is involved in the way the body responds to the 24 hour The capacity-building awards are also fostering day-night cycle. These findings, the result of a large collaborations between whole animal scientists within the international collaboration, were published in Genetics in December 2008. 9 Kay Davies becomes a Yacht racer’s Desert Island Discs castaway urine holds

Aled Jones, the Beatles and Schubert were Reflecting on the secrets of her success, Kay said that nutritional among Professor Dame Kay Davies’ music perseverance and patience are important for a research choices when she joined the ranks of the career – skills she displayed from an early age in primary secrets distinguished and famous who have appeared school. “I loved solving problems” she said, “I was very on BBC Radio 4’s Desert Island Discs. tenacious and would sit in my room until I had finished the Yacht racer Dee Caffari not only made history problem…I am a sticker.” in February by becoming the first woman to Kay, whose many roles include being Director of the MRC sail solo around the world in both directions, Functional Genomics Unit, talked to presenter Kirsty Young Although many hours spent problem-solving in the lab but also took part in MRC research during her on the 15 February broadcast about her life and work, and might leave some people detached from the outcome of latest epic race, by collecting her urine. the music which has been important to her along the way. their research, this is not the case for Kay. She regularly The tracks she chose to take to the fictional desert island meets DMD sufferers and their families at conferences, and Dee spent three months at sea taking part in the Vendée included The Skylark by Aled Jones, a reminder of childhood said that she admires their courage. “They start off playing Globe – a single-handed, non-stop, round-the-world sailing holidays in . Another choice was a recording by a football with their friends and progressively they can’t do race – which she finished in sixth place. Researchers from the group of Kay’s former colleagues from the Institute of that any more. And they’re very innovative in the way MRC Collaborative Centre for Human Nutrition Research in Molecular Medicine, The IMMposters. She recalled hearing they fight the disease and make the best of life…I think Cambridge and from Leeds Metropolitan University set out them play at parties and said they represent “the passion everyone is touched by DMD boys.” to determine Dee’s energy expenditure during the 28,000- of science, and the happiness of the whole place”. mile race to gain more information on the energy needs and The book Kay chose to take to her desert island was Alan calorie intake required in such physically demanding conditions. Over the last 20 years Kay has been unravelling the Bennett’s Untold Stories. And her luxury? “It’s very boring genetic basis of Duchenne Muscular Dystrophy (DMD), a but it has to be a piano because I can be creative…and I During the race, Dee drank doubly-labelled tracer water and devastating muscle wasting disorder affecting boys which can even make up my own tunes”. collected and filtered her urine for five days, storing it for renders them wheelchair bound by the age of 12 and testing later on. Tracer water is slightly heavier than ordinary usually kills them by early adulthood. In the early 1980s she water, which allows scientists to differentiate between the two. developed a simple diagnostic test for screening pregnant By measuring the amount of tracer water Dee excreted in her women who may be at risk. And clinical trials of a new urine at different times, the researchers will be able to target treatment will begin later this year based on her group’s her diet in future to match the different demands of each research into a protein called utrophin, which is similar stage of the race. Dee took measurements at two different to the one absent in DMD. Kay hopes the therapy might stages: the relatively calm Atlantic Ocean leg, and the tougher prevent the disease’s effects if boys are treated as soon as Southern Ocean part of the journey, during which severe wind they are diagnosed with the disease. She told Kirsty she and wave conditions really tested her physical strength. was “really optimistic” that within the next 10 years there would be an effective treatment. MRC Human Nutrition Research’s Antony Wright, who is coordinating the study, said: “The opportunity to measure Kay spoke about the most significant breakthrough of her Dee’s energy expenditure with doubly-labelled water career, which happened on a Sunday morning in 1989. provides us with an improved understanding of the energy She was developing film to find out where a particular costs and dietary requirements of such specialist athletes, gene sequence was localised on the chromosome and and that could directly be used to improve the future discovered another gene that was very similar to the one training regimes of all athletes across a whole spectrum of that is missing in DMD boys – the one encoding utrophin. competitive sporting activities.” “It wasn’t until that ‘eureka’ moment on a Sunday morning that we even dreamt that there might be another gene Dee added: “Mother Nature can be completely unpredictable that might help with the treatment, so we got very, very and definitely challenges you to your maximum, and you just excited about that,” she said. can’t replicate a race like this in a laboratory.” PROFILE The Gray Institute for Radiation, Oncology and Biology, Oxford

Perhaps the best known health statistic you one hospital site. This juxtaposition makes perfect sense; are ever likely to memorise is the one about basic research can work hand-in-hand with the testing of cancer; that around one in three of us will new agents in real patients. get it at some point in our lives. You might look at your friends and family and wonder Directing the institute’s extensive programme of who it could be? You might already know. research is Professor Gillies McKenna. Gillies has Cancer is an indiscriminate killer and while gathered scientific expertise from across the world block DNA repair. It is this weakness that many scientists Clinical scientist Dr Thomas Brunner is looking at mortality rates have decreased in the past (his team also includes researchers from the former at the Gray are now exploiting. If they can block or the effect of a drug called Nelfinavir – an existing 20 years, the incidence rate has increased. Gray Cancer Institute in Northwood and MRC Radiation inhibit the remaining repair systems, the body should be anti-retroviral compound – as a candidate for and Genome Stability Unit at Harwell) to look at ways able to knock out the cancer cells while normal cells will sensitising tumours to radiation. Thomas says: The pressure on NHS resources to deliver a successful to improve cancer treatments using radiation. remain undamaged. “Creating new inhibitor compounds as viable clinical programme of care to each and every cancer patient is interventions can be a lengthy and expensive process. colossal, making financial investment in cancer research He explains: “Tumours must have an Achilles’ heel, a This approach has multiple benefits; the cost and length An approach that circumvents this delay is to adopt to find more efficient and effective methods of treatment weak point – we just have to find it. The focus of of treatments could be vastly reduced; there would drugs currently in clinical use for other diseases that a top health priority. our work here at the Gray is on looking at how the be less patient intervention; and by using drugs rather have the desired effect.” effectiveness of cancer treatments such as radiotherapy than standard cancer treatments such as chemotherapy A collaborative venture can be improved.” (which is toxic to all dividing cells) the side-effects would Thomas is assessing the viability of Nelfinavir as a The Gray Institute for Radiation, Oncology and Biology, be lessened. treatment for advanced pancreatic cancer, a disease that based in the new glass-enveloped Old Road Campus DNA damage signalling has a very poor prognosis. Research Building on the Churchill Hospital site in Our cells are bombarded by damaging factors every day; Professor Thomas Helleday and his group study the Oxford, is one such investment. Its foundations lie in a whether that damage is a result of smoking, sunbathing genes BRCA1 and BRCA2 that predispose women In Phase I clinical trials, Thomas and his team treated scientific initiative to create a world-class research centre or genetic and environmental factors, it will affect our to developing breast and ovarian cancer. Women with 10 advanced pancreatic cancer patients, all of whom for radiobiology that had the capabilities and resources DNA. Cells in the human body have many pathways and defective versions of the genes have up to an 80 per had inoperable tumours, with the drug plus a to explore the translational possibilities of the field. This mechanisms to repair DNA breaks and damage when cent increased risk of developing these cancers. Thomas subsequent course of chemoradiation. The results initiative was a collaborative venture; the Gray, named they occur. If the damage is too great, the cells might self- explains: “In breast and ovarian cancers, a pathway that were startling. Thomas says: “Normally, following a after the English physicist and radiologist, Louis Harold destruct via a process called apoptosis, or their growth repairs mistakes when DNA is replicated no longer course of chemoradiation treatment over many months, Gray, is owned and managed by the and division is halted so that the damage can’t spread. works, and the cancer cells are reliant on a different a pancreatic tumour can be shrunk but not destroyed. Medical Sciences Division with funding from both the process based on a protein called PARP for survival. We Using this inhibitor, compound cancer cell growth was MRC and Cancer Research UK. A common feature of many cancers is that there are have shown that these specific cancers could be targeted slowed and the cells became more sensitive to radiation defects in one or more repair processes which enable using an existing drug that inhibits the PARP protein.” treatment.” The walk from bench to bedside is a short one for the them to dodge these growth controls. Cancer cells Gray’s researchers. The institute is within a stone’s throw get a green light to keep reproducing. Without a stop This concept has now been licensed to AstraZeneca and Of the 10 patients, 60 per cent had tumours that were of the Churchill Hospital – a centre for cancer services signal, they will keep duplicating and eventually a tumour phase II clinical trials of the drug involving a few hundred now resectable, and up to 90 per cent of their tumours and home to one of the busiest oncology departments will form. patients began in May 2007. had been destroyed. In one patient there was 100 per in the UK. The Churchill also houses the new Oxford cent destruction. Two years later, more than half of Cancer Centre, a £109 million project to consolidate However, this genetic damage and the subsequent side- Advanced pancreatic cancer the trial patients are still alive. Thomas is now awaiting cancer services across the city, uniting the main elements stepping from the body’s normal controls on growth The idea of using an existing drug to treat cancers is approval to begin Phase II trials. of cancer diagnosis, investigation and treatment on to may also make them very susceptible to treatments that being adopted by increasing numbers of researchers. 12 13

The process of inhibiting cancer cell growth could be local language, you bring a different perspective and you The future initiative to help experts develop new techniques and applied to many kinds of cancer. Thomas Helleday says: can act as a bridge between the biological and physical There is so much ahead for the Gray Institute, and uses for existing cancer imaging technologies. The MRC “In the future, you could imagine screening a patient’s sciences.” Gillies has high hopes for its future research: “Imaging contributed £3m to the project. cancer for defects, picking out the precise inhibitors to is a key driver behind improvements in the field of target the remaining DNA repair pathways, and treating Tumour microenvironment – metastasis radiation oncology. We want to develop our imaging Secondly, the University of Oxford is to build a new that person’s tumour in a very targeted way.” Non-malignant cells such as inflammatory cells, methods so that clinicians can understand what’s going cyclotron – a particle accelerator – to produce fibroblasts, smooth muscle cells, and endothelial cells on in a tumour without having to touch the patient; radioactive tracers for cancer studies. This project, to Tumour microenvironment – imaging interact with tumour cells and can influence how the in turn this will speed up the processes of diagnoses, which the MRC contributed £2m, will also support work Analogies to Dr Who monsters would not be remiss disease spreads. prognoses and treatment.” at the Gray. when talking about the nature and behaviour of cancer tumours. A rapidly growing tumour cannot feed itself Professor Ruth Muschel’s lab has been using imaging Supporting such research aims does not come cheap but As long as there is cancer, there will be research. And sufficiently and will become starved of oxygen, or techniques to examine the mechanisms that underlie the the institute is at the heart of some significant financial with the life-saving advances being made in research hypoxic. In the hunt for more oxygen and energy, it development of metastases in different organs such as investments. Funding is in place for the development of centres such as the Gray, perhaps that statistic about ‘one can become aggressive and invasive; creating its own the lung, liver and brain. She says: “These methods allow a specialised cancer imaging centre as part of a £50m in three’ is about to change? blood supply and monopolising existing blood vessels. A us to see tumour cells as they interact with blood vessels hypoxic tumour will disperse cancer cells throughout the in their target organs. For example, we can visualise clots body (metastases) and is resistant to chemotherapy and forming around tumour cells and show that inhibition of radiotherapy. these clots can inhibit metastasis. We can also observe the tumour cells exiting from the blood vessels. By Several research groups are investigating how the tumour observing these processes we are gaining a better microenvironment can be improved so that it becomes understanding of how metastatic cells interact with the more susceptible to treatment, so reducing the chance host. This in turn helps us to evaluate targets for therapy of metastasis. Gillies says: “This area of research is one of and for metastasis detection.” RESEARCH CENTRE our greatest strengths and we’re supported by fantastic NEWS imaging and radiation facilities, plus a team of Radiopharmaceuticals experts from across the university; chemists, engineers, An alternative approach to using radiotherapy to kill Dunn reborn as the MRC Mitochondrial Cancer Prevention and Survival (CNC) at the University mathematicians and medics as well as biologists.” cancer cells is to inject radioactive chemicals into the Biology Unit of Cambridge in 2004. Following a strategic review of bloodstream. This method involves using radioisotopes UK nutrition research last year, the MRC has decided to Dr Martin Christlieb is one such expert. A chemist which precisely target the cancer cells; killing them but The MRC Dunn Human Nutrition Unit in Cambridge is transfer the last of these activities to the CNC and to by training, Martin is working on new methods of leaving healthy cells alone. shifting its research focus to work solely on the biology rename the Dunn to reflect its new specialism. assessing tumour oxygenation that can hopefully help of mitochondria, the “powerhouses” inside cells. To mark medics to deliver appropriate treatment regimes to Dr Kate Vallis, who leads the Gray’s Experimental this change it has been renamed The MRC Mitochondrial Unit Director Professor John Walker, who was patients. Martin says: “Two promising imaging techniques Radiation Therapeutics Group, explains: “The drugs we Biology Unit. instrumental in bringing about this new research focus, are PET (positron emission tomography) and SPECT are developing consist of a radioisotope linked to a told Network: “This strategic change acknowledges (single photon emission computed tomography). These protein which is capable of homing in on molecules that The unit’s research includes investigation of how the growing realisation that mitochondrial dysfunction techniques rely on delivery of a radioactive isotope are particularly abundant in cancer cells,” she says. ‘We mitochondria convert energy in the food we eat into fuel is linked with major neurodegenerative and metabolic selectively to the hypoxic tissues so that the presence design the drugs in such a way that they can get into to power the body, how the small DNA molecules in diseases such as Parkinson’s and Alzheimer’s, diabetes and extent of hypoxia can be visualised and measured.” the nucleus of the cancer cell and deliver radioactivity mitochondria are replicated, and how to avoid the effects and obesity, and possibly to the ageing process itself. As directly to the DNA which is then damaged, so that the of reactive oxygen species formed in mitochondria, part of this realignment, the unit will develop its growing The patient is injected with a radioactive isotope that cancer cell dies. We use radioisotopes that emit a type which are implicated in ageing and cancer. interests in the cell biology and genetics of mitochondria is carried to the tumour site. Hypoxic cells trap the of radiation that can only travel a very short distance, and will continue to strengthen its links to basic and isotope, which emits radioactivity that is then picked less than the diameter of a cell. If you can get these drugs Over the last decade the MRC Dunn Human Nutrition translational clinical science.” up by the scanner. A clinician can then establish the into the nucleus they can deliver radiation at that site Unit devoted much of its research to this field, while location and spread of hypoxic areas within the tumour. only and normal surrounding cells will be unaffected.” also looking at how diet can cause or prevent cancer. Professor Walker will lead on the shift in emphasis until Large areas of hypoxia can be bad news and may require The unit moved some of these diet and cancer activities he steps down from being Director in 2011. different management. So what is it like to be a chemist So far, one of the radiopharmaceuticals that Kate’s team across to the Centre for Nutritional Epidemiology in in a biologist’s world? Martin says: “Moving from one has been developing has been tested for safety in breast discipline to another is a very steep learning curve – like cancer patients. Later this year, it will be tested in a doing a second degree and second PhD at the same second trial, this time including patients with cancers of time. On the plus side, once you’ve learned to speak the the head, neck, lung and breast. 15

RESEARCH ROUNDUP

Bad behaviour at school creates lifelong problems Gender divide in Scotland’s alcohol-related deaths Information gathered over 40 years has shown that young people who Twice as many men die every year in Scotland from alcohol misuse than misbehave at school are more likely to experience difficulties in their adult women, research by the MRC Social and Public Health Sciences Unit and lives. Professor Ian Colman and colleagues studied data provided by the the University of Glasgow has revealed. The researchers consolidated MRC Unit for Lifelong Health and Ageing from the MRC National Survey existing data showing that alcohol-related fatalities in both genders have of Health and Development (the 1946 Birth Cohort). They looked at the doubled over the past 10 years, and also found that death rates within health and social problems of over 3,500 people whose behaviour was Scotland vary considerably. The findings show that the men’s death rate rated by their teachers when they were 13 and 15 years old. Later, when from alcohol is 38 per 100,000, while the women’s rate is 16 per 100,000. the participants were aged between 36 and 53, they were asked about their On average, the study found that 999 Scottish men and 448 women die mental health and social and economic status. The study found that those each year from the health consequences of alcohol misuse. The Greater who had severe or mild conduct problems in adolescence were more likely Glasgow area had the highest occurrence of alcohol-related deaths, though to leave school with no qualifications and go on to experience depression, the authors identified areas with high rates in all regions of the country. anxiety, divorce, financial difficulty and other problems in adulthood. This Dr Carol Emslie of the MRC Social and Public Health Sciences Unit, said: result held true even taking into account other factors such as gender, father’s “Although the study shows remarkable differences from place to place social class, adolescent depression and anxiety and cognitive ability. Professor in alcohol-related deaths, the areas in which alcohol-related deaths are a Colman said: “Given the long-term costs to society, and the distressing particular problem for men are largely the same for women. The results impact on the adolescents themselves, our results might have considerable suggest to us that both men and women are vulnerable to the social, implications for public health policy.” economic and cultural pressures which can make people drink too much.”

Published in the British Medical Journal online, January 2009 Published online at www.biomedcentral.com

Sticky antibodies block prion disease Brain feels gain from rival’s pain Antibodies that stick to a brain prion protein called PrP could help Seeing someone we envy suffer misfortune causes increased activity in the prevent prion diseases like variant CJD, research suggests. In part of the brain that processes feelings of reward, research part-funded by infectious prion disease, prions convert naturally-occurring PrP into a the MRC suggests. The research team used functional magnetic resonance corrupted form called PrPSc that has a different shape. PrPSc then builds imaging (fMRI) to measure blood flow to different parts of the brain in a up in the brain, causing the death of brain cells and other symptoms of group of student volunteers. Corresponding images showed which parts of prion disease. Molecular biologists from the MRC Prion Unit at University the brain were busiest when responding to different scenarios. When the College London and biophysicists at the University of Liverpool used most envied student suffered a misfortune, greatest activity was observed in X-ray crystallography to visualise how the antibodies and prion protein the greater ventral striatum, a brain region which perceives reward. The results stuck together at a molecular level. They identified a monoclonal antibody also showed that the part of the brain that deals with thoughts of pain, the which binds very well to PrP and then tested it in cells and in the brains dorsal anterior cingulate cortex (dACC), also processes envy. Activity in the of mice. By sticking to PrP, the antibody prevented the prions from dACC was shown to be greatest the more superior an envied person was converting protein into PrPSc and stopped the prion infection in its tracks. perceived to be. The study was led by Dr Hidehiko Takahashi of Tokyo Medical Professor Samar Hasnain, Professor of Molecular Biophysics and Dental University in Japan. The paper’s co-author, Dr Dean Mobbs of the at the University of Liverpool, said: ‘‘These results are a great example of MRC Cognition and Brain Sciences Unit in Cambridge said: ‘‘These findings research crossing disciplines to share the skills of molecular biologists and frame a theory that envy is a condition in which a person experiences biophysicists to solve problems associated with human disease.’’ cognitive aspects of pain, and that this pain is relieved when something unfortunate happens to an envied person: that is, ‘schadenfreude’ occurs.” Proceedings of the National Academy of Sciences: Advanced online publication Science, 13 February 2009; 323: 5916; 937–939 16 17

MRC Nurturing the PEOPLE therapies of tomorrow

Professor Mark Marsh has been appointed as the new Director of the MRC Laboratory for Molecular Cell Biology (LMCB) and Cell The MRC invested £3 million in seven Professor Charles ffrench-Constant and his team at the Biology Unit at University College London. Having served initially as Acting new awards to support early-stage stem University of Edinburgh will develop an animal model for Director of the unit since March 2006, Mark has now been appointed on cell research in January. The funding will diseases which affect the insulating sheath around nerves, a permanent basis. Mark’s research group at the unit has focused on the bolster the most promising preclinical such as multiple sclerosis. Meanwhile at the University of mechanisms of HIV assembly and how this might be used to understand stem cell research so that it can be Birmingham, Dr Philip Newsome will lead research into and combat HIV infection. He said “I’m very pleased to have been offered advanced more quickly into human trials. transplanting human embryonic stem-cell-derived liver this opportunity – the LMCB is a great research institute and I think cells – which might one day lead to ways of regenerating together we can make it still better.” A team at the University of Oxford led by Dr Paul damaged liver tissue. Fairchild will look at how to avoid immune system The National Osteoporosis Society’s inaugural Duchess of Cornwall Award rejection of transplanted stem cells, which is a serious Other awards will pave the way for future stem cell has been awarded to Professor Cyrus Cooper, Director of the barrier to the use of stem cells in regenerative medicine. transplantation therapy by tracking what happens MRC Epidemiology Resource Centre at Southampton University, for his Using animal models, the team will investigate whether to stem cells which have been transplanted into outstanding contribution to the field of osteoporosis. Professor Cooper the immune system can be persuaded to tolerate the animals. A University of Liverpool-based team will use leads internationally competitive research into the causes of musculoskeletal presence of transplanted stem cells. It will also look at nanoparticles to follow transplanted neural stem cells as disorders, including osteoporosis. He said: “To be recognised with this award the risks of inadvertently transplanting rogue cells which they differentiate to form different parts of the nervous is an incredible honour, and I only hope that my work in the field has made could develop into tumours – and whether or not these system, while at the Institute of Psychiatry in London, a practical difference to people whose lives are affected by osteoporosis.” cells can be sought out and destroyed by the host’s scientists will transplant cells into animal models of Sir Leszek Borysiewicz added his congratulations: “I’m delighted to hear this immune system. Huntington’s disease and then follow their progress using news. The award is a great achievement for Cyrus and the unit, underlining cellular imaging techniques such as fluorescence. the important contribution to osteoporosis that they have all made.”

Professor Sir Philip Cohen, Director of the MRC Protein Phosphorylation Unit in Dundee, has been recognised for his Leading Contribution to Life Sciences in Scotland. Sir Philip received a Scottish Enterprise Life Sciences Award in February at the agency’s 2009 Annual Dinner. Sir Philip recently set up the Scottish Institute for Cell Signalling at the University of Dundee, which he also directs. He is the founder and co-director of the university’s Division of Signal Transduction Therapy which received a Queen’s Anniversary Prize for Higher and Further Education in 2006. Sir Philip said: “I am delighted and honoured to receive this Life Sciences award for my contributions to this field. This award also recognises Top Professor Mark Marsh. Middle The Duchess of Cornwall presenting the extremely high standards and quality of work that is carried out at the Professor Cyrus Cooper with his award. MRC Protein Phosphorylation Unit at the University of Dundee.” Bottom Professor Sir Phillip Cohen (centre) being presented with his award by John Swinney, Finance Minister in the Scottish Government MRC Professor at Liverpool University Ole Petersen has been honoured and Rhona Allison, Senior Director Life Sciences, with the publication of a ‘Festschrift’ – a tribute to his work – by the major Scottish Enterprise. international journal Acta Physiologica. The January 2009 issue of the journal contains a collection of review articles and original articles based on lectures given at a symposium held to mark Professor Petersen’s 65th birthday, at the Royal Danish Academy of Sciences and Letters in Copenhagen. Professor Petersen was the first to identify and characterise calcium-activated ion channels in epithelial cells. He was elected a of The Royal Society in 2000 and was awarded a CBE for Services to Science in 2008. 19

have behaved since the start of the experiment. By On the whole, the pair are very positive about their doing a short-term experiment in just a few animals, experiences of interdisciplinary collaboration. Ben a mathematical equation can be developed which will says: “There were important conceptual insights predict the results of a long-term experiment. imported from physics which have really stretched our understanding, and informed it.” For example, the data Phil says: “The system could also be used in genes which that Ben trawled through had been published in the past, are linked with cancer, to study quantitatively how the but the hidden correlations in it had gone unnoticed until disease would evolve. Since we know what normal is Ben looked at them. Hopping across disciplines from the equation we can see what a cancer gene does that is abnormal. Therefore we’re not just getting data “On the flip side of that, theoretical physicists can’t quicker, but we’re getting data that you could not get any produce their own data, they can only theorise – and solves research puzzle other way.” we can be fickle and cross into any discipline, it doesn’t matter what the data are. I think that biology offers What do you get if you put together a Ben tackled the data with mathematical concepts first Phil and his team are now conducting research into immensely fascinating and brand new problems for a theoretical physicist and a biologist? As it raised by Charles Darwin’s cousin, Sir Francis Galton, who cancer tissue cultures, and hope to be able to use the theoretical physicist to get involved in,” says Ben. turns out, a new way of accurately predicting has a shady reputation as the father of eugenics. Galton new findings even more widely. “We believe this ability to how tissues behave which could lead to considered the probability of having a male heir – an predict is the threshold of a new field in biology which The MRC discipline-hopping grant that supported the new cancer treatments. Network visited the important matter for the Victorian upper classes who could help us to understand processes like ageing, cancer, work was crucial to the collaboration’s success, allowing MRC Cancer Cell Unit at the Hutchison/ wanted to prevent family names from becoming extinct. gene function or drug activity in tissues in a quantitative Ben to simultaneously run another research programme MRC Research Centre in Cambridge to meet A century on, the mathematics that underpinned these way,” he says. in theoretical ultra-cold atom physics at Cambridge an unlikely pairing of scientists which has ideas turned out to be just the job for analysing the University’s . Ben says: “Most of the produced fruitful results. lineage of skin cells. But what were the challenges of approaching the work that’s been done in the last 18 months would not research from two completely different disciplines? Ben have been possible without the effective sabbatical that Six years ago Dr Phil Jones, an oncologist at the MRC Ben explains: “We discovered that all the cells are says: “The main problem is the language barrier – that was provided through the discipline-hopping grant. It Cancer Cell Unit, was working on the genetic labelling equivalent and when they divide they essentially throw requires enormous amounts of patience, flexibility and enabled me to spend all of my time working down here of individual stem cells in mouse skin in the laboratory, the dice, realising a balance between dividing to produce cooperation on both sides. So I’ve been really lucky that at Addenbrooke’s Hospital, mixing with biologists, getting tracking the fate of cells as they divided. After several clones of themselves and differentiation into other cell Phil has indeed been very patient and careful in the way to know much more about these different problems and years he had generated a huge amount of data, but he types. The data showed that with equal probability they that he has explained things.” gave me the opportunity to go outside Cambridge and was stuck on how to interpret it. A colleague of Phil’s may go down a route where they symmetrically self- forge absolutely new collaborations – so I’m enormously happened to mention his problem to her husband, renew or a route where they terminally differentiate.” grateful to the MRC for providing this very valuable grant.” Professor Ben Simons, a theoretical condensed matter physicist with a penchant for statistical analysis. Through Phil adds: “By looking at the fate of hundreds or Read more about Ben and Phil’s research at this serendipitous link, physicist and oncologist began to thousands of cells we were able to write an equation for www.hutchison-mrc.cam.ac.uk/Research/ work together with the support of an MRC discipline- how the tissue keeps itself going, how it maintains itself. Phil_Jones/index.html hopping grant. The equation allows us to predict how cells will behave over a long period – for example a year or six months, Combining their very different skills and backgrounds, with great precision.” Ben and Phil have devised a way of predicting the fate of cells and tissues over a long period, which could cut a By going back to old, previously published data, Ben year’s research down into a couple of weeks, significantly discovered that they had stumbled across a ‘common reduce the amount of animals needed for research, and organisational principle’ which describes how tissue offer new insights into how cancer cells behave. maintains itself in many different organisms and tissue types. So far, he has shown that similar principles holds Until Ben and Phil came together there had been a true not just in mouse skin but also in sperm cells and in long-standing theory that mouse skin was maintained by the cells lining the intestine. a slowly cycling population of stem cells. These stem cells then divide, so the theory went, to produce a transitional The findings could significantly reduce the number of cell population which divides a few times before division animals needed for research. The skin of each animal stops permanently. However, when Ben helped Phil to contains thousands of clusters of labelled cells, the analyse his data, they found out that this wasn’t the case. size of which give accurate information on how cells 20

PUBLIC EVENTS ENGAGEMENT DIARY Dragon’s den for innovative science MRC scientists will get the chance to pitch ideas for translational research projects to a panel of commercial experts on 11 May at an Innovation Afternoon Bringing home being held by MRC Technology. The winner will receive £5,000 towards the research of their lab. The event will take place from 2-5pm at the Laboratory of the relevance of Molecular Biology’s Max Perutz Lecture Theatre and is open to MRC employees or MRC-funded PhD students at MRC research institutes in Cambridge. research www.eventsforce.net/innovation_afternoon The importance of science to people’s Posters win prizes everyday lives and the UK economy is the Research Councils UK is running a poster competition with a difference for subject of a new government campaign Lord Drayson, Sir David Attenborough and Kate early-career researchers funded by the UK research councils. Perspectives gives aimed at the general public and supported Bellingham at the campaign’s researchers the chance to discuss their research with a non-specialist audience, by the UK Research Councils. Downing Street launch event. learn about poster design and explore the social and ethical aspects of their work. Finalists will display their poster at the British Science Festival at the Science: [So what? So everything] was launched by the University of Surrey in September and cash prizes will be awarded for the best Prime Minister at an event at Downing Street in January. posters. The application deadline is 8 May 2009. High profile guests including author Terry Pratchett, www.britishscienceassociation.org/perspectives businessman James Caan and scientist and presenter Kathy Sykes took part in a discussion about how science Edinburgh Science Festival can be taken to a wider audience to encourage more Step inside an MRC Laboratory to create a test-tube baby and examine the DNA public involvement and understanding. to see if it’s a boy or a girl. Or hear how researchers discovered a buried treasure of IQ scores that changed the way we think about intelligence in our lives. These Terry Pratchett said: “Science and its products are in are just two of the exciting activities organised and supported by the MRC at this practically everything we touch, see and do. I use it every year’s Edinburgh Science Festival which runs from 4 to 18 April 2009. day! From my computer, to the medication I take and the www.sciencefestival.co.uk telescope I use – whenever the clouds allow. We have turned ourselves into creatures of science. It is up to us Cheltenham Science Festival to learn how to use science wisely because I don’t think The annual celebration of science takes over Cheltenham Town Hall with its we’ll find such another wonderful resource.” trademark blend of debate, scientific stars and hands-on fun in the interactive Discover Zone. This year’s Guest Director is Carol Vorderman and the festival Science Minister, Lord Drayson, added: “Britain is a world- runs from 3 to 7 June 2009. leader in science, second only to the United States, with www.cheltenhamfestivals.com many of the most important scientific discoveries and inventions having been made here. Continued success Beyond animal research in science is vital to our future – and yet there is still Let your imagination run wild to think about novel ways to replace or reduce the perception among many of our people that science animals in research. The NC3Rs and New Scientist are holding an essay is too clever for them or elitist in some way. We must competition, ‘Beyond animal research’. Entrants should submit a short article on challenge myths like these if we are to build a prosperous, how advances in technology – such as stem cells, tissue engineering or computer science-literate society, able to tackle the difficult issues modelling - could end the need for animal research. Anyone can apply, but entries that modern science presents and work them through to are particularly encouraged from undergraduate, postgraduate and post-doctoral create the jobs and growth of the future.” scientists and science communicators. The closing date is 17 April 2009. www.nc3rs.org.uk/page.asp?id=1022 More information about the campaign can be found at: www.direct.gov.uk/sciencesowhat YOUR What’s new on mrc.ac.uk FEEDBACK Latest podcasts

Translating research into policy in Scotland MRC Network is for anyone who has an interest in the work of the MRC, including scientists, Scottish scientists joined representatives from NHS Health Scotland in doctors and health professionals involved in December at a meeting designed to promote collaboration and stimulate the medical research, government departments translation of scientific findings into government health policy. Hear the views and parliamentarians, and university staff and of a scientist and a policymaker who attended the event. students. The aim is to provide a quick, easy- to-read summary of activities across the MRC, Regeneration research wins Newcomb Cleveland Prize from research news through to funding, grant schemes and policy issues, with pointers to In February, an MRC-funded research team won a prestigious prize for their more in-depth information on websites and in discovery of a single molecular cue that promotes limb regeneration in the other publications. salamander. One of the scientists talks about this exciting discovery from the 2009 American Association for the Advancement of Science conference in We are very keen to receive feedback on Chicago, where the team received their prize. Network and suggestions for new features from our readers. So if you have any comments, To download these and other MRC podcasts, go to: please let us know. Just email: [email protected] www.mrc.ac.uk/Newspublications/Podcasts MRC Network is produced by the MRC You can also read the latest MRC news or subscribe to RSS feeds to receive publications team and is available in print news as it is published at: and in downloadable pdf format at: www.mrc.ac.uk/Newspublications www.mrc.ac.uk

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BOARD Deadline date Board Meeting Molecular and Cellular Medicine 13 May 2009 20 and 21 October 2009 and Immunity 20 May 2009 28 and 29 October 2009 Populations and Systems Medicine 27 May 2009 4 and 5 November 2009 Neurosciences and Mental Health 3 June 2009 12 and 13 November 2009

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